title: Sympatholytic delta-2 opioid receptors moderate ganglionic vasomotor control.
abstract: This study tested the hypothesis that enkephalin increases femoral vascular conductance via the delta-2 phenotype of the opioid receptor (DOR-2) within peripheral sympathetic ganglia. Graded pulses of methionine-enkephalin (ME) were administered (0.03-10 μg/kg) into the terminal aorta of anesthetized dogs proximal to lumbar arteries that perfuse vasomotor ganglia regulating femoral blood flow. Femoral vascular conductance increased sharply (ED50 = 2.6 × 10(-9) mol/kg) accompanied by declines in arterial pressure and femoral vascular resistance. A dose-related increase in arterial pressure preceded each subsequent fall in pressure. The DOR-2 antagonist, naltriben (NTB), abrogated the hyperemic effect of ME (ID50 = 1.4 × 10(-9) mol/kg). DOR-1 blockade (BNTX) was five-fold less effective. The hyperemic effect of ME was also enhanced when sympathetic activity was reflexly increased by bilateral carotid occlusion. The DOR-2 agonist, deltorphin II, produced exaggerated increases in conductance compared with ME that were also reduced by DOR-2 blockade. DOR-1 blockade eliminated the initial pressor responses, exaggerated the subsequent depressor response, increased baseline femoral conductance 10-fold and shifted the ME-mediated hyperemic threshold one dose lower from 0.3 to 0.1 μg/kg, providing indirect support for a competing DOR-1-mediated constriction. Extended exposure to DOR-1 blockade lowered the maximal ME increase in conductance by 30%, suggesting that BNTX reduces the available pool of DOR receptors. In summary, enkephalin mediates a robust hyperemic effect through sympatholytic ganglionic DOR-2 receptors and DOR-1 antagonist studies provide indirect evidence for constituent opposition from a proposed DOR-1-mediated sympathotonic constrictor pathway.
authors.affiliation: Department of Integrative Physiology, Cardiovascular Research Institute, University of North Texas Health Science Center, Fort Worth, 76107, USA.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Barlow
authors.forename: Shekhar H
authors.initials: SH
authors.lastname: Deo
authors.forename: James L
authors.initials: JL
authors.lastname: Caffrey
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004744:Enkephalin, Methionine / Q000008:administration & dosage / Q000378:metabolism; D005263:Femoral Artery / Q000187:drug effects; D005728:Ganglia, Sympathetic / Q000502:physiology*; D006940:Hyperemia / Q000139:chemically induced; D017465:Receptors, Opioid, delta / Q000502:physiology*; D013565:Sympatholytics / Q000008:administration & dosage / Q000378:metabolism; D014666:Vasomotor System / Q000502:physiology*
chemical_list: D017465:Receptors, Opioid, delta; D013565:Sympatholytics; D004744:Enkephalin, Methionine